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Interferon-γ !

  • Molecule

Interferon-γ is the signal that turns macrophages into killers. It is what the blood test for latent tuberculosis (IGRA) measures.

Updated 2026-11-01

What it is

Interferon-γ, the only type II interferon, is made by Th1 cells, CD8 T cells, NK cells and group 1 innate lymphoid cells, mostly in response to IL-12. It binds the IFN-γ receptor (IFNGR1/IFNGR2) and signals through JAK1, JAK2 and STAT1. Its main job is to activate macrophages so they can kill intracellular microbes such as Mycobacterium tuberculosis.

Function

  • Macrophage activation (classical, M1) and granuloma integrity.
  • Better antigen presentation through more MHC class I and II.
  • Stimulates IL-12 production, closing a positive loop with Th1 cells.

Clinical notes

  • Tuberculosis and tuberculoid leprosy: a strong Th1/IFN-γ response contains the bacilli; in lepromatous leprosy the response is weak.
  • IFN-γ receptor, IL12RB1 or STAT1 defects: severe infections with BCG, nontuberculous mycobacteria and Salmonella.
  • Chronic granulomatous disease: recombinant IFN-γ-1b lowers the frequency and severity of serious infections.

In the lab

  • IGRA: blood is exposed to M. tuberculosis antigens and IFN-γ release is measured; BCG vaccination does not cause false positives.
  • IGRA is preferred over the skin test in BCG-vaccinated people (as most people in Colombia are).
  • Neither IGRA nor the skin test separates latent from active tuberculosis; that requires clinical evaluation, chest X-ray and sputum tests.

Test yourself

Think of the answer, then tap the question to see it.

Why is an IGRA not affected by BCG vaccination?

It uses ESAT-6 and CFP-10, antigens present in M. tuberculosis but absent from BCG vaccine strains.

Which cytokine induces IFN-γ production by Th1 and NK cells?

IL-12 from dendritic cells and macrophages.

Can a positive IGRA tell latent from active tuberculosis?

No; it only shows sensitisation to M. tuberculosis. Symptoms, chest X-ray and sputum studies are needed.

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← All of immunology

Educational content on the immune system; not a treatment or individual vaccination guide and no substitute for a health professional's advice. No doses are given.

Sources: IFN-γ-Driven macrophage responses in the immunity to Mycobacterium tuberculosis and Mycobacterium leprae (Frontiers in Cellular and Infection Microbiology, 2025); Updated Guidelines for Using Interferon Gamma Release Assays to Detect Mycobacterium tuberculosis Infection --- United States, 2010 (CDC, MMWR Recommendations and Reports, 2010); Overview of Mendelian Susceptibility to Mycobacterial Diseases (MSMD) (Cureus (PubMed Central), 2025); The Dual Nature of Type I and Type II Interferons (Frontiers in Immunology, 2018).

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Representative model, for educational purposes only.